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  1. Article: [No title information]

    Jorgensen, Christian

    Journal international de bioethique et d'ethique des sciences

    2023  Volume 34, Issue 2, Page(s) 165–171

    Abstract: Cell therapy is becoming established in many fields, including oncology with CAR-Ts or in regenerative medicine for cardiovascular diseases, diabetes or musculoskeletal disorders with mesenchymal stromal cells. These therapeutic cells are called advanced ...

    Title translation Chapitre 12. Impact sociétal et éthique de la thérapie cellulaire et des biotechnologies.
    Abstract Cell therapy is becoming established in many fields, including oncology with CAR-Ts or in regenerative medicine for cardiovascular diseases, diabetes or musculoskeletal disorders with mesenchymal stromal cells. These therapeutic cells are called advanced therapy medicinal products (ATMPs) and include all processes including cells manipulated to obtain reprogramming (iPS), to induce gene expression or by genome editing to modify the expression of a gene. The development of new biomaterial supports that can be 3D printed and take the desired shape of the target tissue before being colonised by the cellular elements necessary for their biological functions and replace the failing organ. All of these new technologies are driving innovation and the development of tomorrow’s bio-medicines. These new biotherapies will profoundly modify patient care in all areas, changing medical practices but with a considerable societal impact. Thus, the development and clinical research on cellular biotherapies are essential health issues but with a major ethical, societal and economic impact.
    MeSH term(s) Humans ; Cell- and Tissue-Based Therapy ; Regenerative Medicine ; Biotechnology ; Medical Oncology
    Language French
    Publishing date 2023-05-26
    Publishing country France
    Document type English Abstract ; Journal Article
    ISSN 2608-1008
    ISSN 2608-1008
    DOI 10.3917/jibes.342.0165
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Mesenchymal Stromal Cells in Osteoarthritis: Evidence for Structural Benefit and Cartilage Repair.

    Song, Yujie / Jorgensen, Christian

    Biomedicines

    2022  Volume 10, Issue 6

    Abstract: Osteoarthritis (OA) presents a major clinical challenge to rheumatologists and orthopedists due to the lack of available drugs reducing structural degradation. Mesenchymal stromal cells (MSCs) may represent new therapeutic approaches in cartilage ... ...

    Abstract Osteoarthritis (OA) presents a major clinical challenge to rheumatologists and orthopedists due to the lack of available drugs reducing structural degradation. Mesenchymal stromal cells (MSCs) may represent new therapeutic approaches in cartilage regeneration. In this review, we highlight the latest knowledge on the biological properties of MSC, such as their chondrogenic and immunomodulatory potential, and we give a brief overview of the effects of MSCs in preclinical and clinical studies of OA treatment and also compare different MSC sources, with the adipose tissue-derived MSCs being promising. Then, we focus on their structural benefit in treating OA and summarize the current evidence for the assessment of cartilage in OA according to magnetic resonance imaging (MRI) and second-look arthroscopy after MSC therapy. Finally, this review provides a brief perspective on enhancing the activity of MSCs.
    Language English
    Publishing date 2022-05-30
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2720867-9
    ISSN 2227-9059
    ISSN 2227-9059
    DOI 10.3390/biomedicines10061278
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  3. Article ; Online: Author Correction: Therapeutic potential in rheumatic diseases of extracellular vesicles derived from mesenchymal stromal cells.

    Bertolino, Giuliana Minani / Maumus, Marie / Jorgensen, Christian / Noël, Danièle

    Nature reviews. Rheumatology

    2024  

    Language English
    Publishing date 2024-04-05
    Publishing country United States
    Document type Published Erratum
    ZDB-ID 2491532-4
    ISSN 1759-4804 ; 1759-4790
    ISSN (online) 1759-4804
    ISSN 1759-4790
    DOI 10.1038/s41584-024-01114-8
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  4. Article ; Online: From self-interest to cooperation: extra-pair mating as a driver of relaxed territorial aggression in social neighbourhoods

    Rumińska, Agnieszka / Jørgensen, Christian / Eliassen, Sigrunn

    Evol Ecol. 2023 Apr., v. 37, no. 2 p.305-325

    2023  

    Abstract: In socially monogamous bird species, males and females tailor their reproductive strategies to that of the other. Interactions are complex, and have elements of both conflict and cooperation. Breeding process is further complicated with the occurrence of ...

    Abstract In socially monogamous bird species, males and females tailor their reproductive strategies to that of the other. Interactions are complex, and have elements of both conflict and cooperation. Breeding process is further complicated with the occurrence of matings outside the pair bond, which is a frequent phenomenon in these species. Extra-pair mating has clear benefits for males, but cuckolded males may withdraw care and resources at a cost to females, which produces an unbalanced costs-to-benefits ratios within the mating pair. We used an individual-based model with social networks approach, to study how female extra-pair mating strategies may affect male investment in offspring care and territorial defence. In our model, extra-pair copulation rate is a female-driven strategy; we use two adjustable male traits—care and territorial defence—that co-evolve with that strategy and control the number of extra-pair copulations initiated by a social female. The model utilises very simple rules of behaviours between individuals that lead to the emergence of evolved changes in mating strategies on a large scale. We show how extra-pair copulations initiated by females in their neighbourhood can reduce territorial defence and wasteful aggression between the males across the whole population. We propose that female mating behaviour and male responses are flexible traits that might serve as potential drivers of the evolution of cooperation.
    Keywords aggression ; birds ; copulation ; evolution ; females ; males ; models ; monogamy ; progeny ; territoriality
    Language English
    Dates of publication 2023-04
    Size p. 305-325.
    Publishing place Springer International Publishing
    Document type Article ; Online
    ZDB-ID 15919-0
    ISSN 1573-8477 ; 0269-7653
    ISSN (online) 1573-8477
    ISSN 0269-7653
    DOI 10.1007/s10682-022-10222-4
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  5. Article: Redefining stem cells through their use in musculoskeletal tissue preservation, regeneration, and cancer metastases to bone.

    Drissi, Hicham / Taipaleenmäki, Hanna / Jorgensen, Christian

    Bone reports

    2023  Volume 19, Page(s) 101678

    Language English
    Publishing date 2023-04-06
    Publishing country United States
    Document type Editorial
    ZDB-ID 2821774-3
    ISSN 2352-1872
    ISSN 2352-1872
    DOI 10.1016/j.bonr.2023.101678
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  6. Article ; Online: An injectable copolymer of fatty acids (ARA 3000 BETA) as a promising treatment for osteoarthritis.

    Toupet, Karine / Jorgensen, Christian / Noël, Danièle

    Scientific reports

    2023  Volume 13, Issue 1, Page(s) 7783

    Abstract: Osteoarthritis (OA) is the most prevalent rheumatic disease and a fast growing cause of disability. Current pharmacological treatments include antalgics and non-steroid anti-inflammatory drugs to control pain and inflammation as well as slow acting drugs ...

    Abstract Osteoarthritis (OA) is the most prevalent rheumatic disease and a fast growing cause of disability. Current pharmacological treatments include antalgics and non-steroid anti-inflammatory drugs to control pain and inflammation as well as slow acting drugs such as intra-articular (IA) administration of hyaluronic acid. Oral supplementation or diet rich in polyunsaturated free fatty acids are proposed but evidence for benefit is still under debate. We here investigated the therapeutic potential of ARA 3000 BETA, an injectable copolymer of fatty acids, at the structural level in OA. Collagenase-induced osteoarthritis model was induced in C57BL/6 mice by collagenase injection into knee joint. Mice were treated with one or two IA or four intra-muscular injections (IM) of ARA 3000 BETA. At sacrifice, knee joints were recovered for cartilage analysis by confocal laser scanning microscopy (CLSM) and bone analysis by micro-computed tomography system. OA histological scoring was performed after safranin O/fast green staining. Histological analysis revealed a protective effect against cartilage degradation in treated knee joints after IM and IA administration. This was confirmed by CLSM with a significant improvement of all articular cartilage parameters, including thickness, volume and surface degradation whatever the administration route. A slight protective effect was also noticed on subchondral bone parameters and knee joint calcification after IM administration and to a lesser extent, two IA injections. We demonstrated the therapeutic efficacy of injectable ARA 3000 BETA in OA with a protection against cartilage and bone alterations providing the proof-of-concept that clinical translation might be envisioned to delay disease progression.
    MeSH term(s) Mice ; Animals ; Fatty Acids/metabolism ; X-Ray Microtomography ; Disease Models, Animal ; Mice, Inbred C57BL ; Osteoarthritis/pathology ; Collagenases/metabolism ; Cartilage, Articular/pathology ; Osteoarthritis, Knee/pathology ; Injections, Intra-Articular
    Chemical Substances Fatty Acids ; Collagenases (EC 3.4.24.-)
    Language English
    Publishing date 2023-05-13
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-023-34206-8
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  7. Article ; Online: Modeling Substrate Entry into the P-Glycoprotein Efflux Pump at the Blood-Brain Barrier.

    Jorgensen, Christian / Ulmschneider, Martin B / Searson, Peter C

    Journal of medicinal chemistry

    2023  Volume 66, Issue 24, Page(s) 16615–16627

    Abstract: We report molecular dynamics simulations of rhodamine entry into the central binding cavity of P-gp in the inward open conformation. Rhodamine can enter the inner volume via passive transport across the luminal membrane or lateral diffusion in the lipid ... ...

    Abstract We report molecular dynamics simulations of rhodamine entry into the central binding cavity of P-gp in the inward open conformation. Rhodamine can enter the inner volume via passive transport across the luminal membrane or lateral diffusion in the lipid bilayer. Entry into the inner volume is determined by the aperture angle at the apex of the protein, with a critical angle of 27° for rhodamine. The central binding cavity has an aqueous phase with a few lipids, which significantly reduces substrate diffusion. Within the central binding cavity, we identified regions with relatively weak binding, suggesting that the combination of reduced mobility and weak substrate binding confines rhodamine to enable the completion of the efflux cycle. Tariquidar, a P-gp inhibitor, aggregates at the lower arms of the P-gp, suggesting that inhibition involves steric hindrance of entry into the inner volume and/or steric hindrance of access of ATP to the nucleotide-binding domains.
    MeSH term(s) ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism ; Blood-Brain Barrier/metabolism ; ATP Binding Cassette Transporter, Subfamily B/metabolism ; Biological Transport ; Rhodamines
    Chemical Substances ATP Binding Cassette Transporter, Subfamily B, Member 1 ; ATP Binding Cassette Transporter, Subfamily B ; Rhodamines
    Language English
    Publishing date 2023-12-14
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 218133-2
    ISSN 1520-4804 ; 0022-2623
    ISSN (online) 1520-4804
    ISSN 0022-2623
    DOI 10.1021/acs.jmedchem.3c01069
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    Zs.B 151: Show issues Location:
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  8. Article ; Online: Musculoskeletal Progenitor/Stromal Cell-Derived Mitochondria Modulate Cell Differentiation and Therapeutical Function.

    Jorgensen, Christian / Khoury, Maroun

    Frontiers in immunology

    2021  Volume 12, Page(s) 606781

    Abstract: Musculoskeletal stromal cells' (MSCs') metabolism impacts cell differentiation as well as immune function. During osteogenic and adipogenic differentiation, BM-MSCs show a preference for glycolysis during proliferation but shift to an oxidative ... ...

    Abstract Musculoskeletal stromal cells' (MSCs') metabolism impacts cell differentiation as well as immune function. During osteogenic and adipogenic differentiation, BM-MSCs show a preference for glycolysis during proliferation but shift to an oxidative phosphorylation (OxPhos)-dependent metabolism. The MSC immunoregulatory fate is achieved with cell polarization, and the result is sustained production of immunoregulatory molecules (including PGE2, HGF, IL1RA, IL6, IL8, IDO activity) in response to inflammatory stimuli. MSCs adapt their energetic metabolism when acquiring immunomodulatory property and shift to aerobic glycolysis. This can be achieved
    MeSH term(s) Animals ; Biomarkers ; Cell Culture Techniques ; Cell Differentiation ; Cell- and Tissue-Based Therapy/methods ; Cellular Reprogramming ; Energy Metabolism ; Humans ; Immunomodulation ; Mesenchymal Stem Cell Transplantation/methods ; Mesenchymal Stem Cells/cytology ; Mesenchymal Stem Cells/metabolism ; Mitochondria/genetics ; Mitochondria/metabolism ; Myoblasts, Skeletal/cytology ; Myoblasts, Skeletal/metabolism ; Oxidation-Reduction ; Reactive Oxygen Species/metabolism ; Signal Transduction
    Chemical Substances Biomarkers ; Reactive Oxygen Species
    Language English
    Publishing date 2021-03-08
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2021.606781
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  9. Article ; Online: In Vitro Human Joint Models Combining Advanced 3D Cell Culture and Cutting-Edge 3D Bioprinting Technologies.

    Jorgensen, Christian / Simon, Matthieu

    Cells

    2021  Volume 10, Issue 3

    Abstract: Joint-on-a-chip is a new technology able to replicate the joint functions into microscale systems close to pathophysiological conditions. Recent advances in 3D printing techniques allow the precise control of the architecture of the cellular compartments ...

    Abstract Joint-on-a-chip is a new technology able to replicate the joint functions into microscale systems close to pathophysiological conditions. Recent advances in 3D printing techniques allow the precise control of the architecture of the cellular compartments (including chondrocytes, stromal cells, osteocytes and synoviocytes). These tools integrate fluid circulation, the delivery of growth factors, physical stimulation including oxygen level, external pressure, and mobility. All of these structures must be able to mimic the specific functions of the diarthrodial joint: mobility, biomechanical aspects and cellular interactions. All the elements must be grouped together in space and reorganized in a manner close to the joint organ. This will allow the study of rheumatic disease physiopathology, the development of biomarkers and the screening of new drugs.
    MeSH term(s) Bioprinting/methods ; Cell Culture Techniques ; Humans ; Organoids/physiopathology ; Osteoarthritis/physiopathology ; Printing, Three-Dimensional
    Language English
    Publishing date 2021-03-08
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells10030596
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  10. Article: Field Portable X-Ray Fluorescence (pXRF) Spectrometry for Chemical Dust Source Characterization: Investigations of Natural and Mining-Related Dust Sources in Greenland (Kangerlussuaq Area)

    Søndergaard, Jens / Jørgensen, Christian Juncher

    Water, air, and soil pollution. 2021 Apr., v. 232, no. 4

    2021  

    Abstract: In this study, we evaluate the use of field portable X-ray fluorescence (pXRF) as a screening tool for dust source characterisation at two sites in Greenland, a natural site near Kangerlussuaq influenced by dust generated by the Greenland Ice Sheet and ... ...

    Abstract In this study, we evaluate the use of field portable X-ray fluorescence (pXRF) as a screening tool for dust source characterisation at two sites in Greenland, a natural site near Kangerlussuaq influenced by dust generated by the Greenland Ice Sheet and an anorthosite mine site located 80 km from Kangerlussuaq. Measurements of ground surface samples were done ex-situ in LDPE plastic bags and in-situ at selected locations. Ex-situ measurements were done both before and after drying of samples to evaluate the effect of water content. Further, the effect of XRF cup films and LDPE bag walls was measured to enable element-specific corrections for signal attenuation of the pXRF measurements. Accuracy and precision were evaluated using a matrix blank and three different soil certified reference materials (CRMs). Finally, pXRF data from the two sites were analysed statistically by principal component analysis (PCA) and linear discriminant analysis (LDA) for the purpose of discriminating between dust sources. The pXRF results showed detectable concentrations of the elements: Al, Si, K, Ca, Fe, Sr, Zr and Ba in all samples (and P, Mn, Zn, Rb, Y, Nb, Ta, Pb and Th in some samples). Moreover, the results showed good accuracies for 21 elements in the CRMs. The PCA/LDA plots based on the pXRF data provided a good tool to discriminate between natural and mining-related dust sources and also between some specific mining-related sources. Altogether, this demonstrates that pXRF combined with multivariate statistics can be an adequate tool for fast cost-effective dust source characterisation.
    Keywords X-radiation ; air ; cost effectiveness ; discriminant analysis ; dust ; fluorescence ; ice ; multivariate analysis ; principal component analysis ; soil ; soil pollution ; water ; water content ; Greenland
    Language English
    Dates of publication 2021-04
    Size p. 144.
    Publishing place Springer International Publishing
    Document type Article
    Note NAL-AP-2-clean
    ZDB-ID 120499-3
    ISSN 1573-2932 ; 0049-6979 ; 0043-1168
    ISSN (online) 1573-2932
    ISSN 0049-6979 ; 0043-1168
    DOI 10.1007/s11270-021-05095-2
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